We propose to organize two further Critical Assessment of Genome Interpretation (CAGI) conferences, in 2017 and 2018. The CAGI experiments and conferences are providing the primary independent assessment of the state of the art of variation interpretation. In the CAGI experiments participants are provided genetic variants and make blinded predictions of resulting molecular, cellular, organismal, or clinical phenotypes. The new experiments will build on extensive and informative results obtained in the first four rounds. Datasets will include rare disease, common diseases, and germline and somatic cancer variation, from both research and clinical sources. Data types will include complete genomes and exomes, as well as single base changes affecting coding sequence, gene expression, and RNA splicing. Independent assessors will evaluate the predictions against experimentally characterized phenotypes. A CAGI Conference is held at the end of each experiment. The specific goals of the conferences are: (1) to assess the quality of current computational methods for interpreting genomic data, and highlight innovations and progress; (2) to guide future research efforts in computational genome interpretation and build a strong community for collaboration and interaction; and (3) to disseminate results both amongst key members of the variant-phenotype prediction community at the meeting and to a broader audience via publication of results in peer-reviewed journals. The new CAGI experiments will continue the process already established over four rounds, starting in 2010 and with the latest meeting in March 2016. The 2016 experiment yielded 174 submissions on 11 challenges, by 37 groups from 13 countries. 57 people attended the meeting, and we are disseminating results via open access publications and conference presentations. Once again, the participating community was overwhelmingly of the opinion that this experiment is necessary and should be organized again on an ongoing basis. The organizers will continue to encourage the participation of women and underrepresented minorities, and broad participation of trainees and senior scientists at the CAGI conferences. Funding is requested for awarding 17 trainee fellowships for students and postdoctoral researchers to cover registration and approximately 2/3 of their other participation costs. In addition, we seek funding to subsidize registration and approximately half of meeting costs of the independent assessors, some data providers, and the organizers of the CAGI experiments.